JPH08239351A - Intermediate used in production of 6-hydroxy-3-pyridinecarboxylic acid ester and its production - Google Patents
Intermediate used in production of 6-hydroxy-3-pyridinecarboxylic acid ester and its productionInfo
- Publication number
- JPH08239351A JPH08239351A JP8018197A JP1819796A JPH08239351A JP H08239351 A JPH08239351 A JP H08239351A JP 8018197 A JP8018197 A JP 8018197A JP 1819796 A JP1819796 A JP 1819796A JP H08239351 A JPH08239351 A JP H08239351A
- Authority
- JP
- Japan
- Prior art keywords
- formula
- compound
- acid ester
- production
- hydroxy
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D213/78—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D213/79—Acids; Esters
- C07D213/803—Processes of preparation
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D213/78—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D213/79—Acids; Esters
- C07D213/80—Acids; Esters in position 3
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pyridine Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Abstract
Description
【０００１】本発明は、６−ヒドロキシ−３−ピリジン
カルボン酸エステルの新規製造を行なうのに用いること
のできる新規中間生成物、及びかかる中間生成物の製造
方法に関する。６−ヒドロキシ−３−ピリジンカルボン
酸エステルは公知であり、殺虫剤（insecticides）を製
造するための中間生成物として用いることができる。The present invention relates to a new intermediate product which can be used for carrying out a new production of 6-hydroxy-3-pyridinecarboxylic acid ester, and a process for producing such an intermediate product. 6-Hydroxy-3-pyridinecarboxylic acid esters are known and can be used as intermediate products for the production of insecticides.
【０００２】６−ヒドロキシ−３−ピリジンカルボン酸
エステルはオキシこはく酸エステルを発煙硫酸と加熱
し、得られるクマリン酸誘導体をアンモニアと反応させ
ることにより得ることができることは既に公知である。
この反応の欠点は比較的大量の発煙硫酸を用いることで
あり、これは仕上げ中に再び反応混合物から除去しなけ
ればならず、経済的取扱いが容易でない（Ber．１７、
２３８４（１８８４）、Helv．Chim．Acta ４、４８２
（１９２１）及びJ．Am．Chem．Soc．６６、１４８２
（１９４４）参照）。It is already known that 6-hydroxy-3-pyridinecarboxylic acid ester can be obtained by heating an oxysuccinic acid ester with fuming sulfuric acid and reacting the resulting coumarinic acid derivative with ammonia.
The disadvantage of this reaction is that it uses a relatively large amount of fuming sulfuric acid, which has to be removed again from the reaction mixture during finishing and is not easy to handle economically (Ber. 17 ,
2384 (1884), Helv. Chim. Acta 4 , 482
(1921) and J. Am. Chem. Soc. 66 , 1482
(See 1944)).
【０００３】更に、６−ヒドロキシ−３−ピリジンカル
ボン酸エステルとその対応する互変異性体のα−ピリド
ンカルボン酸エステルが、エナミン誘導体を非プロトン
性極性希釈剤と１６０℃〜１９０℃の温度にて反応させ
ることにより製造できることが公知である。この方法の
欠点は、比較的高い反応温度とそれに起因する高いエネ
ルギー消費である（Tetrahedron、第６２３〜６３２頁
（１９７４）参照）。In addition, 6-hydroxy-3-pyridinecarboxylic acid ester and its corresponding tautomeric α-pyridonecarboxylic acid ester can be used to bring an enamine derivative to an aprotic polar diluent at a temperature of 160 ° C to 190 ° C. It is known that it can be produced by reacting with The disadvantage of this method is the relatively high reaction temperature and the resulting high energy consumption (see Tetrahedron, pp. 623-632 (1974)).
【０００４】今回、一般式（I）This time, the general formula (I)
【０００５】[0005]
【化４】 [Chemical 4]
【０００６】式中、Ｒはアルキルを表わす、の６−ヒド
ロキシ−３−ピリジンカルボン酸エステルが、式（II）Wherein 6 represents a 6-hydroxy-3-pyridinecarboxylic acid ester of the formula (II)
【０００７】[0007]
【化５】 Embedded image
【０００８】式中、Ｒは上記の意味を有し、及びＲ1は
低級アルキルを表わす、の１−ジアルキルアミノ−１．
３−ブタジエン−２，４−ジカルボン酸エステルを、
（ａ）アルカリ金属アルコラートの存在下及び希釈剤の
存在下で０℃〜１２０℃の温度にて気体アンモニアと反
応させるか、又は（ｂ）二段階反応で、希釈剤の存在下
で０℃から希釈剤の沸点までの温度にて気体アンモニア
と反応させて式（III）Wherein R has the meaning given above and R 1 represents lower alkyl, 1-dialkylamino-1.
3-butadiene-2,4-dicarboxylic acid ester,
(A) reacting with gaseous ammonia in the presence of an alkali metal alcoholate and in the presence of a diluent at a temperature of 0 ° C to 120 ° C, or (b) in a two-step reaction in the presence of a diluent from 0 ° C. Reaction with gaseous ammonia at temperatures up to the boiling point of the diluent to give formula (III)
【０００９】[0009]
【化６】 [Chemical 6]
【００１０】式中、Ｒは上記の意味を有する、のアミノ
誘導体を得、適当ならば得られる式（III）の化合物を
単離し、次いで式（III）のアミノ誘導体を第２段階で
希釈剤の存在下０℃〜１２０℃の温度にてアルカリ金属
アルコラートと反応させて化合物（I）を得る、方法に
より得られることが見出された。## STR1 ## where R has the abovementioned meaning, an amino derivative of ## STR1 ## is obtained, where appropriate the compound of formula (III) is isolated, and then the amino derivative of formula (III) is used in a second step as a diluent. It was found to be obtainable by a method of reacting with an alkali metal alcoholate in the presence of to obtain a compound (I) at a temperature of 0 ° C to 120 ° C.
【００１１】驚くべきことに、式（I）の化合物は、上
記方法（方法（ａ）及び（ｂ））により良好な収率で簡
単な方法で及び安価な新規中間生成物から出発して製造
することができる。Surprisingly, the compounds of the formula (I) are prepared by the above-mentioned processes (processes (a) and (b)) in good yields in a simple manner and starting from inexpensive new intermediate products. can do.
【００１２】式（I）中、ＲがＣ1〜Ｃ6−アルキルを表
わす化合物が、上記方法により好ましく製造される。Compounds of formula (I) in which R represents C 1 -C 6 -alkyl are preferably prepared by the process described above.
【００１３】式（I）中、ＲがＣ1〜Ｃ4−アルキルを表
わす化合物が、上記方法により特に好ましく製造され
る。Compounds of formula (I) in which R represents C 1 -C 4 -alkyl are particularly preferably prepared by the process described above.
【００１４】式（I）の化合物は好ましくは方法（ａ）
(“一段階法"）により製造される。The compound of formula (I) is preferably process (a).
(“One-step method”).
【００１５】方法（ａ）にて上記方法の出発物質とし
て、１−ジメチルアミノ−１，３−ブタジエン−２，４
−ジカルボン酸ジエチル、アンモニア及びナトリウムエ
チラートを用いるならば、該方法は下式In the method (a), the starting material for the above method is 1-dimethylamino-1,3-butadiene-2,4.
If diethyl dicarboxylate, ammonia and sodium ethylate are used, the process is
【００１６】[0016]
【化７】 [Chemical 7]
【００１７】により表わすことができる。Can be represented by
【００１８】方法（ｂ）にて上記方法の出発物質として
１−ジメチルアミノ−１，３−ブタジエン−２，４−ジ
カルボン酸ジエチル及びアンモニアを用い、生成する１
−アミノ−１，３−ブタジエン−２，４−ジカルボン酸
ジエチルを単離し、このエステルを更にナトリウムエチ
ラートと反応させるならば、該反応順序は下式Formed in process (b) using diethyl 1-dimethylamino-1,3-butadiene-2,4-dicarboxylate and ammonia as starting materials for the above process 1
If amino-diethyl-1,3-butadiene-2,4-dicarboxylate is isolated and this ester is further reacted with sodium ethylate, the reaction sequence is
【００１９】[0019]
【化８】 Embedded image
【００２０】により表わすことができる。Can be represented by
【００２１】式（II）は上記方法（方法（ａ）及び
(ｂ))の出発物質として用いることのできる１−ジアル
キルアミノ−１，３−ブタジエン−２，４−ジカルボン
酸エステルの一般的定義を与える。この式中、Ｒは好ま
しくは式（I）の置換基の定義に関して好ましいか又は
特に好ましいとして上記した基を表わす。この式中のＲ
1は好ましくはＣ1〜Ｃ6−アルキルを表わす。Ｒ1は特に
好ましくはＣ1〜Ｃ4−アルキルを表わす。Formula (II) is the above method (method (a) and
This gives a general definition of 1-dialkylamino-1,3-butadiene-2,4-dicarboxylic acid esters which can be used as starting materials for (b)). In this formula, R preferably represents the radicals mentioned above as being preferred or particularly preferred in the definition of the substituents of the formula (I). R in this formula
1 preferably represents C 1 -C 6 -alkyl. R 1 particularly preferably represents C 1 -C 4 -alkyl.
【００２２】式（II）の化合物は新規である。これら
は、例えば、式（IV） ＲＯＯＣ−ＣＨ＝ＣＨ−ＣＨ２−ＣＯＯＲ (IV) 式中、Ｒは上記の意味を有する、のグルタコン酸エステ
ルを、適当ならば酸無水物、例えば無水酢酸、の存在下
及び適当ならば不活性希釈剤、例えばトルエン、の存在
下で０℃〜４０℃の温度にて、式（V） （Ｒ1）2Ｎ−ＣＨ（ＯＲ2）2 （V） 式中、Ｒ1は上記の意味を有し、及びＲ2は低級アルキル
を表わす、のＮ，Ｎ−ジアルキルホルムアミドアセター
ルと反応させる方法により簡単に製造することができ
る。The compounds of formula (II) are new. These include, for example, in the formula (IV) ROOC-CH = CH -CH 2 -COOR (IV) formula, R represents a glutaconic acid ester, have the meanings given above, acid anhydrides, if appropriate, for example acetic anhydride, Of the formula (V) (R 1 ) 2 N—CH (OR 2 ) 2 (V) in the presence of and, if appropriate, an inert diluent, for example toluene, at a temperature of 0 ° C. to 40 ° C. Wherein R 1 has the above-mentioned meaning and R 2 represents lower alkyl, and can be simply prepared by a method of reacting with N, N-dialkylformamide acetal.
【００２３】式（IV）は出発物質として用いられるべき
グルタコン酸エステルの一般的定義を与える。この式
中、Ｒは好ましくは式（I）の置換基の定義に関して好
ましいか又は特に好ましいとして上記した基を表わす。Formula (IV) gives a general definition of glutaconate esters to be used as starting materials. In this formula, R preferably represents the radicals mentioned above as being preferred or particularly preferred in the definition of the substituents of the formula (I).
【００２４】式（IV）のグルタコン酸エステルは有機化
学の公知化合物である。The glutaconates of formula (IV) are known compounds of organic chemistry.
【００２５】式（IV）化合物の記載できる例は、グルタ
コン酸ジメチル、ジエチル、ジ−ｎ−プロピル、ジ−ｉ
−プロピル及びジ−ｎ−ブチルである。Illustrative examples of compounds of formula (IV) are dimethyl glutaconate, diethyl, di-n-propyl, di-i.
-Propyl and di-n-butyl.
【００２６】式（V）は式（II）の新規化合物の製造の
出発物質として更に用いられるべきＮ，Ｎ−ジアルキル
ホルムアミドアセタールの一般的定義を与える。この式
（V）中、Ｒ1及びＲ2は好ましくはＣ1〜Ｃ6−アルキル
を表わし、特に好ましくはＣ1〜Ｃ4−アルキルを表わ
す。Formula (V) provides a general definition of N, N-dialkylformamide acetals which should be further used as starting material for the preparation of the novel compounds of formula (II). In this formula (V), R 1 and R 2 preferably represent C 1 -C 6 -alkyl, particularly preferably C 1 -C 4 -alkyl.
【００２７】式（V）のＮ，Ｎ−ジアルキルホルムアミ
ドアセタールは有機化学の一般に公知の化合物である。The N, N-dialkylformamide acetals of formula (V) are generally known compounds of organic chemistry.
【００２８】式（V）の化合物の記載できる例は、Ｎ，
Ｎ−ジメチルホルムアミドジメチルアセタール、Ｎ，Ｎ
−ジメチルホルムアミドジエチルアセタール、Ｎ，Ｎ−
ジメチルホルムアミドジ−ｎ−プロピルアセタール、
Ｎ，Ｎ−ジメチルホルムアミドジ−ｉ−プロピルアセタ
ール及びＮ，Ｎ−ジメチルホルムアミドジ−ｎ−ブチル
アセタールである。Ｎ，Ｎ−ジメチルホルムアミドジメ
チルアセタールが本新規化合物の製造の反応成分として
好ましく用いられる。Illustrative examples of compounds of formula (V) are N,
N-dimethylformamide dimethyl acetal, N, N
-Dimethylformamide diethyl acetal, N, N-
Dimethylformamide di-n-propyl acetal,
N, N-dimethylformamide di-i-propyl acetal and N, N-dimethylformamide di-n-butyl acetal. N, N-dimethylformamide dimethyl acetal is preferably used as a reaction component in the production of the novel compound.
【００２９】式（III）は、上記方法（方法（ｂ）／第
２段階）の出発物質として用いられるべきアミノ誘導体
の一般的定義を与える。この式中、Ｒは好ましくは式
（I）の置換基の定義に関して好ましいか又は特に好ま
しいとして上記した基を表わす。Formula (III) gives a general definition of the amino derivative to be used as the starting material for the above method (method (b) / second step). In this formula, R preferably represents the radicals mentioned above as being preferred or particularly preferred in the definition of the substituents of the formula (I).
【００３０】式（III）の化合物は本発明に従う新規な
化合物である。これらは上記方法（方法（ｂ）、第１段
階）により簡単に製造することができる。The compounds of formula (III) are new compounds according to the invention. These can be easily produced by the above method (method (b), first step).
【００３１】式（III）のアミノ誘導体の記載できる例
は、１−アミノ−１，３−ブタジエン−２，４−ジカル
ボン酸ジメチル、ジエチル、ジ−ｎ−プロピル、ジ−ｉ
−プロピル及びジ−ブチルである。Illustrative examples of amino derivatives of formula (III) are dimethyl 1-amino-1,3-butadiene-2,4-dicarboxylate, diethyl, di-n-propyl, di-i.
-Propyl and di-butyl.
【００３２】式（I）の化合物の製造方法は好ましくは
不活性有機溶媒を用いて行なわれる。ここでは方法
（ａ）に好ましい可能な希釈剤は芳香族炭化水素、例え
ばキシレン、トルエン及びベンゼンである。The process for preparing the compounds of formula (I) is preferably carried out using an inert organic solvent. Possible diluents preferred here for process (a) are aromatic hydrocarbons such as xylene, toluene and benzene.
【００３３】方法（ｂ）の第１及び第２段階に好ましい
可能な希釈剤は低級アルコール、例えばメタノール、エ
タノール、ｎ−プロパノール、ｉ−プロパノール、ｎ−
ブタノール、ｉ−ブタノール、sec.−ブタノール及びte
rt.−ブタノールである。Preferred possible diluents for the first and second stages of process (b) are lower alcohols such as methanol, ethanol, n-propanol, i-propanol, n-.
Butanol, i-butanol, sec.-butanol and te
rt.-butanol.
【００３４】方法（ａ）及び（（ｂ）／段階２）に好ま
しい可能なアルカリ金属アルコラートは、ナトリウム及
びカリウムメチラート及びエチラート並びにカリウムte
rt.−ブチラートである。ナトリウムメチラート及びエ
チラートが特に好ましく用いられる。The preferred possible alkali metal alcoholates for processes (a) and ((b) / step 2) are sodium and potassium methylates and ethylates and potassium te.
rt.-butyrate. Sodium methylate and ethylate are particularly preferably used.
【００３５】上記方法（方法（ａ）及び（ｂ））では反
応温度は実質的範囲内で可変である。反応は一般に、方
法（ａ）及び（（ｂ）／段階２）では０℃〜１２０℃の
温度にて、好ましくは２０℃〜１００℃の温度にて、及
び方法（（ｂ）／段階１）では０℃から希釈剤の沸点ま
での温度にて、好ましくは０℃〜５０℃の温度にて、よ
り好ましくは１０℃〜３５℃の温度にて行なわれる。上
記方法は好ましくは常圧下で行なわれる。In the above methods (methods (a) and (b)), the reaction temperature is variable within a substantial range. The reaction is generally in processes (a) and ((b) / step 2) at temperatures between 0 ° C. and 120 ° C., preferably at temperatures between 20 ° C. and 100 ° C. and in process ((b) / step 1). Is performed at a temperature from 0 ° C to the boiling point of the diluent, preferably at a temperature of 0 ° C to 50 ° C, and more preferably at a temperature of 10 ° C to 35 ° C. The above method is preferably carried out under normal pressure.
【００３６】上記方法（方法（ａ））を行なうにあた
り、式（II）の化合物１モル当り１〜１．５モル、好ま
しくは１〜１．３モルのアルカリ金属アルコラート及び
２〜１０モル、好ましくは３〜６モルの気体アンモニア
を用いる。一般に、アンモニアをアルコラートとアルコ
ールの溶液中に通して飽和させる手順を行なう。次いで
式（II）の化合物を該溶液に加え、混合物を必要な温度
で数時間撹拌する。式（I）の化合物を遊離させるため
に、ｐＨ値４になるように濃塩酸を加える。更なる仕上
げは通例の方法により行なう。In carrying out the above method (method (a)), 1 to 1.5 mol, preferably 1 to 1.3 mol, of alkali metal alcoholate and 2 to 10 mol, preferably 1 to 10 mol, per mol of the compound of formula (II) are used. Uses 3 to 6 moles of gaseous ammonia. Generally, a procedure is performed in which ammonia is saturated by passing it through a solution of alcoholate and alcohol. Then the compound of formula (II) is added to the solution and the mixture is stirred at the required temperature for several hours. To release the compound of formula (I), concentrated hydrochloric acid is added to a pH value of 4. Further finishing is done by customary methods.
【００３７】上記方法（方法（ｂ））を行なうにあた
り、第１段階では式（II）の化合物１モル当り２〜１０
モル、好ましくは３〜６モルの気体アンモニアを用い
る。一般に、アンモニアをアルコールに通し、この混合
物に必要量の式（II）の化合物を加え、該混合物を必要
な温度で数時間撹拌する手順を行なう。行ない得るあら
ゆる仕上げ及び式（III）の化合物の単離の後、第２段
階では１モルの式（III）の化合物をアルコール及び１
〜１．５モル、好ましくは１〜１．３モルのアルコラー
トの存在下で必要な温度にて数時間撹拌する手順を行な
う。式（I）の化合物の遊離させるために、ｐＨ値４に
なるように濃塩酸を加える。仕上げは通例の方法で行な
う。In carrying out the above method (method (b)), in the first step, 2 to 10 per mol of the compound of the formula (II) is used.
Molar, preferably 3-6, mol of gaseous ammonia is used. Generally, ammonia is passed through an alcohol, the required amount of compound of formula (II) is added to this mixture, and the mixture is stirred at the required temperature for several hours. After any work-up possible and isolation of the compound of formula (III), the second step is to add 1 mol of the compound of formula (III) to alcohol and 1
The procedure of stirring for several hours at the required temperature in the presence of ~ 1.5 mol, preferably 1-1.3 mol of alcoholate is carried out. To liberate the compound of formula (I), concentrated hydrochloric acid is added to a pH value of 4. Finishing is done in the usual way.
【００３８】上記方法により製造されるべき式（I）の
６−ヒドロキシ−３−ピリジンカルボン酸エステルは、
殺虫剤としての作用を有するニトロメチレン誘導体を製
造するための中間生成物として用いることができる（欧
州特許Ａ−１６３，８５５号及び欧州特許Ａ−１９２，
０６０号参照）。The 6-hydroxy-3-pyridinecarboxylic acid ester of formula (I) to be produced by the above method is
It can be used as an intermediate product for producing a nitromethylene derivative having an insecticidal action (European Patents A-163,855 and European Patent A-192).
No. 060).
【００３９】式（I）の化合物を公知の殺虫剤にする更
なる過程は、例えば下式：Further processes for converting compounds of formula (I) into known insecticides are described, for example, by the following formula:
【００４０】[0040]
【化９】 [Chemical 9]
【００４１】によって例示することができる。Can be illustrated by
【００４２】参考例 １ Reference Example 1
【００４３】[0043]
【化１０】 [Chemical 10]
【００４４】［方法（ａ）］６ｇ（０．０２５モル）の
１−ジメチルアミノ−１，３−ブタジエン−２，４−ジ
カルボン酸ジエチルを、５０ｍｌのエタノール中の２．
１ｇ（０．１２モル）のアンモニアガス及び２．０４ｇ
（０．０３モル）のナトリウムエチラートの溶液に５℃
にて加え、その混合物を還流下で１８時間沸騰させる。
次いで溶媒を真空中で留去し、残留物を６０ｍｌの水に
溶かし、濃塩酸を加えて混合物をｐＨ４にもっていき、
各々５０ｍｌの塩化メチレンで３回抽出する。有機相を
硫酸ナトリウムで乾燥し、真空中で蒸発させる。[Method (a)] 6 g (0.025 mol) of diethyl 1-dimethylamino-1,3-butadiene-2,4-dicarboxylate was added to 2. ml of 50 ml of ethanol.
1 g (0.12 mol) of ammonia gas and 2.04 g
To a solution of (0.03 mol) sodium ethylate at 5 ° C.
And boil the mixture under reflux for 18 hours.
Then the solvent was distilled off in vacuo, the residue was dissolved in 60 ml of water and concentrated hydrochloric acid was added to bring the mixture to pH 4,
Extract 3 times with 50 ml of methylene chloride each. The organic phase is dried over sodium sulphate and evaporated in vacuo.
【００４５】このようにして３．６ｇ（理論の８６％）
の６-ヒドロキシ−３−ピリジンカルボン酸エチルが融
点１４３℃〜１４４℃のベージュ色の結晶として得られ
る。In this way 3.6 g (86% of theory)
Ethyl 6-hydroxy-3-pyridinecarboxylate is obtained as beige crystals with a melting point of 143 ° C-144 ° C.
【００４６】［方法（ｂ）］０．７５ｇ（０．０１１モ
ル）のナトリウムエチラート、１５ｍｌのメタノール及
び２．１ｇ（０．０１モル）の１−アミノ−１，３−ブ
タジエン−２，４−ジカルボン酸ジエチルの混合物を還
流下で１８時間沸騰させる。次いで溶媒を真空中で留去
し、残留物を２０ｍｌの水に溶かし、塩酸を加えて溶液
をｐＨ４にもっていく。それを各々１００ｍｌの塩化メ
チレンで３回抽出し、有機相を硫酸ナトリウムで乾燥
し、溶媒を真空中で留去する。[Method (b)] 0.75 g (0.011 mol) of sodium ethylate, 15 ml of methanol and 2.1 g (0.01 mol) of 1-amino-1,3-butadiene-2,4. Boil a mixture of diethyl dicarboxylate under reflux for 18 hours. Then the solvent is distilled off in vacuo, the residue is dissolved in 20 ml of water and hydrochloric acid is added to bring the solution to pH 4. It is extracted 3 times with 100 ml of methylene chloride each time, the organic phase is dried over sodium sulphate and the solvent is distilled off in vacuo.
【００４７】１．４ｇ（理論の８４％）の６−ヒドロキ
シ−３−ピリジンカルボン酸エチル（融点１４４℃）が
得られる。1.4 g (84% of theory) of ethyl 6-hydroxy-3-pyridinecarboxylate (melting point 144 ° C.) are obtained.
【００４８】以下の式（I）の化合物が記載した参考例
１及び方法（ａ）及び（ｂ）の２つの方法と同様にして
製造できる。The following compounds of formula (I) can be prepared in the same manner as in the two methods of Reference Example 1 and methods (a) and (b).
【００４９】[0049]
【化１１】 [Chemical 11]
【００５０】参考例 ２ Reference Example 2
【００５１】[0051]
【化１２】 [Chemical 12]
【００５２】融点：１４７℃参考例 ３ Melting point: 147 ° C. Reference example 3
【００５３】[0053]
【化１３】 [Chemical 13]
【００５４】参考例(II−１) ［式(II)の出発化合物の
製造］ Reference Example (II-1) [Production of Starting Compound of Formula (II)]
【００５５】[0055]
【化１４】 Embedded image
【００５６】２５．４ｇ（０．２１モル）のジメチルホ
ルムアミドジメチルアセタールを、２８ｇ（０．１８モ
ル）のグルタコン酸ジメチル、３６．７ｇ（０．３６モ
ル）の無水酢酸及び２００ｍｌのトルエンの混合物に一
滴ずつ加える。この間に該反応混合物は約２７℃に暖ま
る。これを冷却せずに１８時間撹拌し、次いで５０℃に
て真空中で留去する。残留物を高真空下８０℃にて揮発
成分を追い出す。25.4 g (0.21 mol) of dimethylformamide dimethyl acetal were added to a mixture of 28 g (0.18 mol) of dimethyl glutaconate, 36.7 g (0.36 mol) of acetic anhydride and 200 ml of toluene. Add each drop. During this time the reaction mixture warms to about 27 ° C. It is stirred for 18 hours without cooling and then distilled off in vacuo at 50 ° C. The residue is stripped of volatiles under high vacuum at 80 ° C.
【００５７】３０ｇ（理論の７８％）の１−ジメチルア
ミノ−１，３−ブタジエン−２，４−ジカルボン酸ジメ
チルが融点６２℃のベージュ色の結晶形で得られる。30 g (78% of theory) of dimethyl 1-dimethylamino-1,3-butadiene-2,4-dicarboxylate are obtained in beige crystalline form with a melting point of 62 ° C.
【００５８】以下の式（II）の化合物が参考例（II−
１）と同様に製造できる。The following compound of formula (II) is used in Reference Example (II-
It can be manufactured in the same manner as 1).
【００５９】[0059]
【化１５】 [Chemical 15]
【００６０】参考例（II−２） Reference Example (II-2)
【００６１】[0061]
【化１６】 Embedded image
【００６２】ｎD 23：１．５７１５参考例（II−３） N D 23 : 1.5715 Reference example (II-3)
【００６３】[0063]
【化１７】 [Chemical 17]
【００６４】参考例（II−４） Reference Example (II-4)
【００６５】[0065]
【化１８】 Embedded image
【００６６】実施例（III−１）［式(III)の出発化合物
の製造］ Example (III-1) [Production of Starting Compound of Formula (III)]
【００６７】[0067]
【化１９】 [Chemical 19]
【００６８】２．１ｇ（０．１２５モル）のアンモニア
ガスを５０ｍｌのエタノールに溶かす。６ｇ（０．０２
５モル）の１−ジメチルアミノ−１，３−ブタジエン−
２，４−ジカルボン酸ジエチルをこの混合物に加え、該
反応混合物を還流下２４時間沸騰させる。次いで溶媒を
真空中で留去し、残留物を石油エーテルで摩砕し、結晶
生成物を吸引濾別する。2.1 g (0.125 mol) of ammonia gas are dissolved in 50 ml of ethanol. 6 g (0.02
5 mol) of 1-dimethylamino-1,3-butadiene-
Diethyl 2,4-dicarboxylate is added to this mixture and the reaction mixture is boiled under reflux for 24 hours. Then the solvent is distilled off in vacuo, the residue is triturated with petroleum ether and the crystalline product is filtered off with suction.
【００６９】４．５ｇ（理論の８４％）の１−アミノ−
１，３−ブタジエン−２，４−ジカルボン酸ジエチルが
融点１０９℃のベージュ色の結晶形で得られる。4.5 g (84% of theory) of 1-amino-
Diethyl 1,3-butadiene-2,4-dicarboxylate is obtained in beige crystalline form with a melting point of 109 ° C.
【００７０】以下の式（III）の化合物が実施例（III−
１）と同様に製造できる。The following compounds of the formula (III) are prepared in the Example (III-
It can be manufactured in the same manner as 1).
【００７１】[0071]
【化２０】 Embedded image
【００７２】実施例（III−２） Example (III-2)
【００７３】[0073]
【化２１】 [Chemical 21]
【００７４】融点：１５１℃実施例（III−３） Melting point: 151 ° C. Example (III-3)
【００７５】[0075]
【化２２】 [Chemical formula 22]
Claims (2)
式（II） 【化３】 式中、 Ｒは上記の意味を有し、及びＲ1は低級アルキルを表わ
す、の１−ジアルキルアミノ−１，３−ブタジエン−
２，４−ジカルボン酸エステルを希釈剤の存在下０℃か
ら希釈剤の沸点までの温度にて気体アンモニアと反応さ
せることを特徴とする方法。2. Formula (III): Wherein R represents lower alkyl,
Formula (II) embedded image 1-dialkylamino-1,3-butadiene-in which R has the meaning given above and R 1 represents lower alkyl.
A method which comprises reacting a 2,4-dicarboxylic acid ester with gaseous ammonia in the presence of a diluent at a temperature from 0 ° C. to the boiling point of the diluent.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE19863640583 DE3640583A1 (en) | 1986-11-27 | 1986-11-27 | METHOD FOR PRODUCING 6-HYDROXY-3-PYRIDINE CARBONIC ACID ESTERS |
| DE3640583.3 | 1986-11-27 |
Related Parent Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP62292210A Division JP2517735B2 (en) | 1986-11-27 | 1987-11-20 | Method for producing 6-hydroxy-3-pyridinecarboxylic acid ester |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPH08239351A true JPH08239351A (en) | 1996-09-17 |
| JP2713873B2 JP2713873B2 (en) | 1998-02-16 |
Family
ID=6314933
Family Applications (3)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP62292210A Expired - Lifetime JP2517735B2 (en) | 1986-11-27 | 1987-11-20 | Method for producing 6-hydroxy-3-pyridinecarboxylic acid ester |
| JP8018240A Expired - Lifetime JP2713874B2 (en) | 1986-11-27 | 1996-01-10 | Intermediate used for producing 6-hydroxy-3-pyridinecarboxylic acid ester and method for producing the same |
| JP8018197A Expired - Lifetime JP2713873B2 (en) | 1986-11-27 | 1996-01-10 | Intermediate used for producing 6-hydroxy-3-pyridinecarboxylic acid ester and method for producing the same |
Family Applications Before (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP62292210A Expired - Lifetime JP2517735B2 (en) | 1986-11-27 | 1987-11-20 | Method for producing 6-hydroxy-3-pyridinecarboxylic acid ester |
| JP8018240A Expired - Lifetime JP2713874B2 (en) | 1986-11-27 | 1996-01-10 | Intermediate used for producing 6-hydroxy-3-pyridinecarboxylic acid ester and method for producing the same |
Country Status (5)
| Country | Link |
|---|---|
| US (1) | US4849519A (en) |
| EP (1) | EP0268964B1 (en) |
| JP (3) | JP2517735B2 (en) |
| DE (2) | DE3640583A1 (en) |
| HU (1) | HU202496B (en) |
Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4968803A (en) * | 1989-04-10 | 1990-11-06 | Allied-Signal Inc. | Process for the preparation of 2-hydroxypyridine or quinoline compounds |
| US5475131A (en) * | 1993-01-19 | 1995-12-12 | Bayer Aktiengesellschaft | Process for the preparation of a mixture of aminomethylenated glutaconic acid dinitriles |
| CN109134285A (en) * | 2018-09-17 | 2019-01-04 | 枣庄学院 | A kind of α substituted beta-unsaturation amino acid esters compound and preparation method |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB867930A (en) * | 1958-11-12 | 1961-05-10 | Wallace & Tiernan Inc | Substituted pyridones |
-
1986
- 1986-11-27 DE DE19863640583 patent/DE3640583A1/en not_active Withdrawn
-
1987
- 1987-11-06 US US07/118,364 patent/US4849519A/en not_active Expired - Fee Related
- 1987-11-14 DE DE8787116841T patent/DE3770128D1/en not_active Expired - Lifetime
- 1987-11-14 EP EP87116841A patent/EP0268964B1/en not_active Expired - Lifetime
- 1987-11-20 JP JP62292210A patent/JP2517735B2/en not_active Expired - Lifetime
- 1987-11-27 HU HU875353A patent/HU202496B/en not_active IP Right Cessation
-
1996
- 1996-01-10 JP JP8018240A patent/JP2713874B2/en not_active Expired - Lifetime
- 1996-01-10 JP JP8018197A patent/JP2713873B2/en not_active Expired - Lifetime
Also Published As
| Publication number | Publication date |
|---|---|
| DE3770128D1 (en) | 1991-06-20 |
| EP0268964B1 (en) | 1991-05-15 |
| HUT48215A (en) | 1989-05-29 |
| JP2713874B2 (en) | 1998-02-16 |
| JPS63141968A (en) | 1988-06-14 |
| HU202496B (en) | 1991-03-28 |
| DE3640583A1 (en) | 1988-06-16 |
| JP2713873B2 (en) | 1998-02-16 |
| EP0268964A1 (en) | 1988-06-01 |
| JP2517735B2 (en) | 1996-07-24 |
| US4849519A (en) | 1989-07-18 |
| JPH08239352A (en) | 1996-09-17 |
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